Translating terpenes
Terpene-based natural products represent some of the most complex molecular scaffolds known, yet they are generated from surprisingly simple hydrocarbon precursors. Terpene cyclases catalyze a key step in the formation of these structurally diverse systems, creating rings and chirality from achiral terpene starting materials. However, the mechanisms of these enzymes are difficult to decipher, in part because the reactive carbocation intermediates are capable of significant rearrangements that may or may not be controlled by the active site. Hong et al. examined the non-enzymatic interconversion between intermediates in one such reaction—the conversion of copalyl diphosphate to abietadiene by abietadiene synthase. By performing intrinsic reaction coordinate calculations, the authors followed the re-arrangement of one putative intermediate through two high-energy transition states yielding two possible products with different molecular architectures. Because each of these products is directly downhill from this bifurcation point, both products should be produced in the absence of enzyme intervention. These results raise the possibility that the off-pathway product may be produced by an as-yet undiscovered enzyme and also provide new insights as to how biosynthetic enzymes might be manipulated to create chemical diversity. (Nat. Chem. 1, 384–389, 2009) CG
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